Journal
VIROLOGY
Volume 398, Issue 2, Pages 273-279Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.12.024
Keywords
Merkel cell polyomavirus; Large T antigen; Merkel cell carcinoma; Nuclear localization signal; Mutation
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [C-21590520]
- Ministry of Health, Labor and Welfare [H21-AIDS-Ippan-006, H20-Nanchi-Ippan-035, H20-Shinko-Ippan-006, H21-Shinko-Ippan-009]
- Japan Health Sciences Foundation [SAA4832]
- Grants-in-Aid for Scientific Research [21590520] Funding Source: KAKEN
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To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases. (C) 2009 Elsevier Inc. All rights reserved.
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